Gas7 Is Required for Mesenchymal Stem Cell-Derived Bone Development

Chao, Chuck C.‐K.; Hung, Feng‐Chun; Chao, Jack J.

doi:10.1155/2013/137010

Cited by 16 publications

(11 citation statements)

References 42 publications

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“…Prostaglandin-endoperoxide synthase 2 ( PTGS2 or COX-2 ) was down-regulated in chronic inflammation [23], whose inhibitors are considered as a potential risk factor for bone healing [24]. In the meanwhile, growth-arrest-specific 7 gene ( GAS7 ) is required for osteoblast differentiation [25], which may play a role in bone manifestations in SAPHO syndrome. Besides, a feedback loop between inflammation and Zn uptake has been observed in rheumatoid arthritis [26], while Zn transporters, also known as SLC30 families, are related to different skin disorders [27] as well as systemic inflammatory response syndrome [28].…”

Section: Resultsmentioning

confidence: 99%

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

Sun

Zhu

et al. 2019

Orphanet J Rare Dis

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Background SAPHO syndrome is a rare disease characterized by inflammatory lesions on skin and bones. Diversified manifestation and inadequate understanding of etiology has limited its diagnosis and treatment. The co-occurrence of other immune-mediated diseases strongly suggests an involvement of autoimmunity in SAPHO syndrome. However, the role of the largest population of circulating immune cells, neutrophils, is still not well explored. In this study, we performed RNA sequencing to profile the mRNA expression of neutrophils purified from peripheral blood of SAPHO patients to identify key genes associated with SAPHO syndrome, trying to find new functional molecules or biomarkers for this rare disease. Results A total of 442 differentially expressed genes were identified ( p < 0.05, fold change > 2), in which 294 genes were upregulated and 148 genes were downregulated. Five differentially expressed genes of interest were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), among which S100A12 was upregulated and positively related to high-sensitivity C-reactive protein (hsCRP), while the downregulated gene MYADM was positively related to osteocalcin. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes were enriched in “systemic lupus erythematosus” and “ECM-receptor interaction”. Gene ontology (GO) enrichment showed that differentially expressed genes may participate in biological processes such as “cell migration” and “cell adhesion”. Conclusions In conclusion, this study provides a first insight into transcriptome characteristics of SAPHO syndrome, indicating an over-active neutrophil recruitment in patients and possibly suggesting molecular candidates for further study on diagnosis and pathology of this disease. Electronic supplementary material The online version of this article (10.1186/s13023-019-1169-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

Sun

Zhu

et al. 2019

Orphanet J Rare Dis

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“…In the mouse embryo, levels of GAS7 decrease as the embryo grows, except in neuronal-specific epidermal cells, in which expression remains high ( Moorthy et al 2005 ). GAS7 expression also plays an essential role in other nonneuronal growth functions, such as osteoblast differentiation and bone development ( Chao et al 2013 ). Furthermore, neural outgrowth and arborization are shared functions between the exocyst and GAS7 ( Martin-Urdiroz et al 2016 ; You and Lin-Chao 2010 ), whereas TNFAIP2 expression has been associated with some neurodegenerative conditions ( Brohawn et al 2016 ; Colangelo et al 2002 ).…”

Section: Discussionmentioning

confidence: 99%

Cadmium-Associated Differential Methylation throughout the Placental Genome: Epigenome-Wide Association Study of Two U.S. Birth Cohorts

Everson

Punshon

Jackson

et al. 2018

Environ Health Perspect

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Background:Cadmium (Cd) is a ubiquitous environmental toxicant that can accumulate in the placenta during pregnancy, where it may impair placental function and affect fetal development.Objectives:We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM) and associations with gene expression; we also aimed to identify novel pathways involved in Cd-associated reproductive toxicity.Methods:Using placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an epigenome-wide association study (EWAS) between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth size metrics.Results:We identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values<1×10−5, two of which were within a 5% false discovery rate (FDR). DNAM levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA. Higher placental expression of TNFAIP2 and ACOT7 and lower expression of RORA were associated with lower birth weight z-scores (p-values<0.05).Conclusion:Cd-associated differential DNAM and corresponding DNAM-expression associations were observed at loci involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2, ACOT7, and RORA) were also associated with birth weight, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity. https://doi.org/10.1289/EHP2192

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“…The GAS7 protein consists of a series of different functional domains: Src homology 3 domain (SH3), WW domain, and FES-CIP4 homology (FCH) domain from the N-terminal to the C-terminal. Among these functional domains, the SH3 domain is present only in the GAS7C isoform [ 7 ]. SH3 domains are able to bind to proline-rich ligands and change the subcellular localization of the bound protein.…”

Section: Introductionmentioning

confidence: 99%

Growth-arrest-specific 7C protein inhibits tumor metastasis via the N-WASP/FAK/F-actin and hnRNP U/β-TrCP/β-catenin pathways in lung cancer

et al. 2015

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Growth-arrest-specific 7 (GAS7) belongs to a group of adaptor proteins that coordinate the actin cytoskeleton. Among human GAS7 isoforms, only GAS7C possesses a Src homology 3 domain. We report here that GAS7C acts as a migration suppressor and can serve as a prognostic biomarker in lung cancer. GAS7C overexpression reduces lung cancer migration, whereas GAS7C knockdown enhances cancer cell migration. Importantly, ectopically overexpressed GAS7C binds tightly with N-WASP thus inactivates the fibronectin/integrin/FAK pathway, which in turn leads to the suppression of F-actin dynamics. In addition, overexpression of GAS7C sequesters hnRNP U and thus decreases the level of β-catenin protein via the β-TrCP ubiquitin-degradation pathway. The anti-metastatic effect of GAS7C overexpression was also confirmed using lung cancer xenografts. Our clinical data indicated that 23.6% (25/106) of lung cancer patients showed low expression of GAS7C mRNA which correlated with a poorer overall survival. In addition, low GAS7C mRNA expression was detected in 60.0% of metastatic lung cancer patients, indicating an association between low GAS7C expression and cancer progression. A significant inverse correlation between mRNA expression and promoter hypermethylation was also found, which suggests that the low level of GAS7C expression was partly due to promoter hypermethylation. Our results provide novel evidence that low GAS7C correlates with poor prognosis and promotes metastasis in lung cancer. Low GAS7C increases cancer cell motility by promoting N-WASP/FAK/F-actin cytoskeleton dynamics. It also enhances β-catenin stability via hnRNP U/β-TrCP complex formation. Therefore, GAS7C acts as a metastasis suppressor in lung cancer.

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Gas7 Is Required for Mesenchymal Stem Cell-Derived Bone Development

Cited by 16 publications

References 42 publications

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

Cadmium-Associated Differential Methylation throughout the Placental Genome: Epigenome-Wide Association Study of Two U.S. Birth Cohorts

Growth-arrest-specific 7C protein inhibits tumor metastasis via the N-WASP/FAK/F-actin and hnRNP U/β-TrCP/β-catenin pathways in lung cancer

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